Hydroxyl Group and Vasorelaxant Effects of Perillyl Alcohol, Carveol, Limonene on Aorta Smooth Muscle of Rats

Abstract

The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory effect on the contraction induced by electromechanical and pharmacomechanical coupling. In the case of LM, but not CV and POH, this effect was influenced by preservation of the endothelium. POH and CV but not LM exhibited greater pharmacological potency on BayK-8644-induced contraction and on electromechanical coupling than on pharmacomechanical coupling. In endothelium-denuded preparations, the order of pharmacological potency on electrochemical coupling was LM < CV < POH. These compounds inhibited also, with grossly similar pharmacological potency, the contraction induced by phorbol ester dibutyrate. The present results suggest that LM, CV and POH induced relaxant effect on vascular smooth muscle by means of different mechanisms likely to include inhibition of PKC and IP3 pathway. For CV and POH, hydroxylated compounds, it was in electromechanical coupling that the greater pharmacological potency was observed, thus suggesting a relative specificity for a mechanism likely to be important in electromechanical coupling, for example, blockade of voltage-dependent calcium channel.

Relaxant Effect of Monoterpene (−)-Carveol on Isolated Human Umbilical Cord Arteries and the Involvement of Ion Channels

“…Our data differ from what has been found for carveol on rat aorta, where a greater pharmacological potency was observed in the presence of K + [12]. However, it is noteworthy that differences in response can occur both between vessels from experimental animals (rodents) and humans, which may be due to distinctions between them in terms of physiology, types of receptors and the action of certain signaling pathways [15,23,28].…”

“…Corroborating with our findings, Cardoso-Teixeira et al [12] demonstrated that carveol promoted relaxation in rat aortic preparations that were pre-contracted with BayK-8644. This suggests that this monoterpene may be acting by inhibition of L-type Ca 2+ channels, since BayK-8644 is an agonist in L-type Ca 2+ channels [38].…”

“…Carveol, a natural monoterpene used in increasing and cumulative concentrations of 1 to 5000 µM, altered the HUA tone in a relaxant manner, demonstrating a vasorelaxant effect in the presence of contractions evoked by 5-HT and K + , as well as demonstrating the involvement of L-type Ca 2+ channels as well as the partial contribution of voltage-dependent K + channels. These results also corroborate the vasorelaxant effects of carveol observed in rat aortas [12].…”

“…However, it is noteworthy that differences in response can occur both between vessels from experimental animals (rodents) and humans, which may be due to distinctions between them in terms of physiology, types of receptors and the action of certain signaling pathways [15,23,28]. Given that studies suggest little participation of endothelium-dependent factors in the vasorelaxant effect of HUAs [28], only preparations from Cardoso-Teixeira et al [12], which were devoid of an endothelium, were used as a comparative value where the effect of carveol on HUAs had been previously evaluated.…”

Effects of Terpenes and Terpenoids of Natural Occurrence in Essential Oils on Vascular Smooth Muscle and on Systemic Blood Pressure: Pharmacological Studies and Perspective of Therapeutic Use

“…Among the most prominent and therapeutically potentially promising activities of natural monoterpenes and monoterpenoids are those on the cardiovascular system [6]. Reports on literature, here reviewed and discussed, reveal their effect on heart (rate and inotropism), systemic blood pressure (SBP), and blood vessels (direct (myogenic) and indirect (endothelium mediated)) [7][8][9][10].…”